Up to now, the targeted genetic engineering of microorganisms has concentrated largely on the modification of structural genes encoding enzymes in metabolic pathways. This has been done either by up- or down-regulation of gene expression or by modification of kinetic characteristics, substrate specificity or regulatory properties of the constituent enzymes (Nevoigt, 2008). However, targeted engineering has shown only limited success when it comes to complex traits determined by multiple genes and largely unknown regulatory networks. In fact, evolutionary engineering has often been used as a strategy to address such phenotypes difficult to engineer in a rational way. In addition, attempts have been made to engineer regulatory factors in order to simultaneously and randomly alter the regulation of many genes at a time.